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Selenoprotein Depletion in Mice

Selenoproteins play essential roles in both development and adulthood, mainly through their functions in balancing cellular redox levels. Because selenoproteins require a trace micronutrient and specialized translational machinery, however, they seem ill-suited to handle rapid or drastic changes in redox state.

Model for the compensatory gene induction by Nrf2 in the absence of selenoprotein production.

In this Paper of the Week, Takafumi Suzuki and colleagues examine how cells cope with selenoprotein depletion that may be brought on by dietary deficiencies in selenium or translational inhibition by statin drugs. They developed a conditional knock-out mouse for the selenocysteine tRNA gene (Trsp) and observed that Trsp deletion in macrophages or liver resulted in the induction of several cytoprotective agents to counter the elevated oxidative stress. The up-regulated antioxidants, which include glutathione S-transferase P1 and NAD(P)H quinone oxidoreductase 1, are known targets of the transcription factor Nrf2, and mice with a double knock-out of Trsp and Nrf2 displayed a severely compromised cytoprotective response, increased cellular apoptosis, and a reduced survival rate. These results reveal that the Nrf2 gene battery acts as a rapid response agent to assist or replace selenoprotein activity when necessary.

FOOTNOTES

See referenced article, J. Biol. Chem. 2008, 283, 2021-2030

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